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About Malaria PowerPoint Presentation

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Description : WHAT IS MALARIA? MALARIA IS MORE DEADLIER etc.

Tags : MALARIA,mosquito,disease of humans,MALARIA TRANSMISSION

Published on : Aug 20, 2020 | Views : 3542 | Downloads : 36

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MEDICAL ASPECTS
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A mosquito-borne infectious disease of humans & other animals Caused by parasitic protozoans (a type of unicellular microorganism) of the genus Plasmodium Commonly transmitted via a bite from an infected female Anopheles mosquito & introduces the organisms from its saliva into the person's circulatory system In the blood, the protists travel to the liver to mature & reproduce WHAT IS MALARIA?
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MALARIA IS MORE DEADLIER No. 3 killer infectious disease in the world WHO estimates that 3,000 people die from malaria in Africa every day, mostly women & children Unlike influenza, we have no vaccine against malaria Now resistance to the MOST effective anti-malarial Artemisinin is being reported Kills one child every 20 seconds
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TRANSMISSION Bite of Infected Female Anopheles Mosquito Blood transfusion Congenital Sharing needles
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EASY UNDERSTANDING OF MALARIA MALARIA is a parasitic infection that leads to the destruction of RBCs
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Malaria is an acute infectious disease Causative agent : Plasmodium species Protozoan parasite 4 species infecting humans P. falciparum P. vivax P. malariae P. ovale Transmitted by female Anopheles mosquito Is characterized by high fever with rigor, anaemia, profuse sweating EASY UNDERSTANDING OF MALARIA
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TYPES OF MALARIA
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SPECIES INFECTING HUMANS 4 species of plasmodium typically cause human malaria: Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium ovale A 5th species, P knowlesi- a pathogen of monkeys, but has recently been recognized to cause illness in humans in Asia All of the species may cause significant illness P falciparum is responsible for majority of serious complications & deaths
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SYMPTOMS OF MALARIA
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LIFE CYCLE OF MALARIAL PARASITE
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ANTI MALARIAL EVOLUTION
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Therapeutic classification Chemical classification CLASSIFICATION OF ANTIMALARIAL DRUGS
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THERAPEUTIC CLASSIFICATION Causal prophylaxis: (Primary tissue schizonticides) Destroy parasite in liver cells & prevent invasion of erythrocytes Primaquine, proguanil Supressive Prophylaxis: Supress the erythrocytic phase & thus attack of malarial fever can be used as prophylactic Chloroquine, proguanil, mefloquine, doxycycline
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Clinical cure: erythrocytic schizonticides Used to terminate an episode of malarial fever Fast acting, high efficacy Chloroquine, quinine, mefloquine, atovaquone, artemisinin Slow acting, low efficacy drugs Proguanil, pyrimethamine, sulfonamides, tetracyclines THERAPEUTIC CLASSIFICATION
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Radical curatives: Used in relapsing malaria Eradicate all forms of P. vivax & P. ovale from the body Suppressive drugs + hypnozoito cidal drugs For vivax: primaquine 15 mg daily for 14 days Gametocidal: Destroy gametocytes and prevent transmission Primaquine, artemisinin – against all plasmodia Chloroquine, Quinine – Pl Vivax Proguanil , pyrimethamine – prevent development of sporozoites THERAPEUTIC CLASSIFICATION
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CHEMICAL CLASSIFICATION 4 aminoquinolines - Chloroquine, Hydroxychloroquine, Amodiaquine, Pyronaridine 8 aminoquinolines - Primaquine, Tafenoquine, Bulaquine Cinchona alkaloids - Quinine, Quinidine Quinoline methanol - Mefloquine Biguanides - Proguanil, Chlorproguanil Diaminopyrimidines - Pyrimethamine Tetracyclines - tetracycline, doxycycline Naphthoquinone - Atovaquone Sesquiterpene lactones - Artesunate, artemether, arteether, Dihydroartemisinin Mannich base: pyronaridine Amino alcohols: halofantrine, lumefantrine
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DRUGS USED IN MALARIA Tissue schizontocides- drugs eliminating developing or dormant liver forms Blood schizontocides- drugs acting on erythrocytic parasites Gametocides- drugs that kill sexual stages and prevent transmission to mosquitoes
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FORMS OF ANTIMALARIAL DRUGS Clinically malarial infections can be controlled by the drugs used in following ways: Causal prophylaxis Suppressive prophylaxis Clinical cure Radical cure Gametocidal
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CAUSAL PROPHYLAXIS Drugs prevent the maturation of or destroy the sporozoites within the infected hepatic cell- thus prevent erythrocytic invasion Primaquine – for all species of malaria but not used due to its toxic potential Proguanil- primarily for P. falciparum and not effective against P. vivax (weak activity), rapid development of resistance
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SUPPRESSIVE PROPHYLAXIS Schizontocides inhibit erythrocyte phase and prevent the rupture of the infected erythrocytes, lead to freedom from rigors and pyrexia Includes quinine, chloroquine, proguanil, pyrimethamine, artemicinin and tetracycline
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CLINICAL CURE Erythrocytic schizontocides are used to terminate episodes of malarial fever Fast acting high efficacy drugs: Chloroquine, quinine, mefloquine, halofantrine, artemicinin Used singly to treat malaria fever Faster acting, preferably used in falciparum malaria where delayed treatment may lead to death even if parasites are clear from blood Slow acting low efficacy drugs: Proguanil, pyrimethamine, sulfonamides, tetracyclines Used only in combination
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RADICAL CURE Drug attack exoerythrocytic stage (hypnozoites) given with clinical curative for the total eradication of the parasite from the patient’s body Radical cure of the P. falciparum malaria can be achieved by suppressives only For radical cure of P.vivax infection, primaquine & proguanil are effective
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GAMETOCIAL Removal of male and female gametes of Plasmodia formed in the patient’s blood It has no benefit for treated patient Primaquine and artemisinins are highly effective against gametocytes of all species
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CHLOROQUINE Rapidly acting erythrocytic schizontocide against all species of Plasmodia Drug of choice for treating acute attacks caused by sensitive strains of P. vivax or P. falciparum Controls most clinical attack in 1-2days with disappearance of parasite from peripheral blood in 1-3days No effect on exo- erythrocytic phase Neither prevent primary infection nor relapse in P. vivax and P.ovale Drug of choice for use in pregnancy, prophylaxis Cholroquine prevents the polymerization to hemozoin The accumulation of heme results in lysis of both the parasite and the red blood cell
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CHLOROQUINE ADVERSE EFFECTS CNS- mild headache, confusion, psychosis, convulsion, impaired hearing Eye (with high dose)- loss of vision due to retinal damage, reversible corneal damage GIT- Nausea, vomiting, anorexia, epigastric pain, diarrhea( can be minimized by taking with meal) Skin- uncontrolled itching, urticaria, exfoliative dermatitis Parenteral administration- Hypotension, cardiac arrhythmias, cardiac depression
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MEFLOQUINE (MQ) Fast acting erythrocytic(blood) schizontocide but slower than CQ or quinine Effective against CQ-sensitive as well as resistant Plasmodia Efficacious suppressive prophylactic for multi-resistant P. Falciparum Accumulates in infected RBCs, binds to heme and this complex damages the parasite’s membrane Long half life (17days)
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MQ is bitter in taste At high doses: Nausea, vomiting, diarrhea, abdominal pain,bradycardia Ataxia, hallucinations, depression MQ is safe in pregnancy Rare events of toxicity are seen Contraindicated - in patients with anxiety, depression, psychosis, and in cardiac conduction defects Use is restricted due to its toxicity, cost and long half life MEFLOQUINE ADVERSE EFFECTS
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QUININE Quinine is a l-isomer of alkaloid obtained from cinchona bark and quinidine (antiarrhythmic) is its d-isomer An effective erythrocytic schizontocide as suppressive and used to prevent or terminate attacks of vivax, ovale, malariae, sensitive falciparum Moderately effective against hepatic form (pre- exoerythrocyte and gametocytes)
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QUININE ADVERSE EFFECTS Cinchonism: Higher dose symptoms include nausea, vomiting, tinnitus, vertigo, headache, mental confusion, difficulty in hearing and visual defects, diarrhea, flushing Rapid i.v. injection: Hypotension and cardiac arrhythmias Can cause profused hypoglycemia Pregnancy: Causes abortion in early pregnancy by stimulating myometrium and premature labor by stimulating uterus Hypoglycaemia
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PROGUANIL (CHLOROGUANIDE) Slow acting erythrocytic schizontocide Cyclized in body to a triazine derivative(cycloguanil) Cycloguanil inhibits plasmodial dihydrofolate reductase (DHFRase) Resistance developed due to mutational changes in the plasmodial DHFRase enzyme Half life 16-20 hour ; noncumulative
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PROGUANIL ADVERSE EFFECTS Mild abdominal upset, vomiting Occasional stomatitis Haematuria, rashes and transient loss of hair Note : Safe during pregnancy
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PRIMAQUINE Poor erythrocytic schizontocide Has marked effect on primary and secondary hepatic phases of malarial parasite Highly active against gametocytes and hypnozoites Intermediate act as oxidant that are responsible for the schizontocial action
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Abdominal pain, gastrointestinal upset, weakness or uneasiness chest Leucopenia (high dose) Hemolysis Methaemoglobinaemia Tachypnoea -abnormally rapid breathing. Cyanosis - bluish discoloration of the skin due to poor circulation or inadequate oxygenation of the blood. Should not be given during pregnancy because fetus is glucose-6-phosphate dehydrogenase ( G-6-PD) deficient PRIMAQUINE ADVERSE EFFECTS
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ARTEMISININ Artemisinin is the active principle of the plant Artimisia annua - A chinese traditional plant Sesquiterpine lactone derivative Most potent & rapid acting blood schizonticides Short duration of action High recrudescence rate Poorly soluble in water & oil Converted to dihydroartemisinin, which is a potent antimalarial compound
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ARTEMISININ DERIVATIVES Short elimination half life led to the search for the derivatives with improved pharmacological properties & better antimalarial activity Artesunate: Water soluble, useful for oral I/V, I/M & rectal administration Artemether : Lipid soluble, useful for oral I/M & rectal administration Arteether Artemether & artesunate are prodrugs converted to dihydroartemisinin responsible for activity
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MECHANISM OF ACTION Contain endoperoxide bridge which interacts with heme in parasite Heme iron cleaves this endoperoxide bridge Generation of highly reactive free radicals which damage parasite membrane by covalently binding to membrane proteins
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ANTIMALARIAL ACTION Mainly schizonticides & are effective against P vivax & chloroquine resistant & sensitive strains of P falciparum Useful in cerebral malaria & MDR MALARIA
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Also known as dihydroqinghaosu, artenimol or DHA Active metabolite of all artemisinin compounds (artemisinin, artesunate, artemether, etc.) and is also available as a drug in itself Highly effective against blood schizonts of both malarial parasites P. falciparum & P. vivax. A semi-synthetic derivative of artemisinin & is widely used as an intermediate in the preparation of other artemisinin-derived antimalarial drugs Used to treat malaria, generally as a combination drug with piperaquine The recommended dose for dihydroartemisinin is 120 mg initially, then 60 mg daily for a further 4 to 6 days. DIHYDROARTEMISININ
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A bisquinoline first made in the 1960s, and used extensively in China and Indochina as prophylaxis and treatment attacks the blood stages of Plasmodium Interferes with the parasites ability to form hemozion – the detoxified form of ferriprotoporphyrin (FPIX) from haemoglobin digestion Characterized by slow absorption & a long biological half-life, making it a good partner drug with artemisinin derivatives which are fast acting but have a short biological half-life Developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurually similar antimalarial drug chloroquine. Due to widespread parasite resistance to piperaquine, the drug fell out of use as a monotherapy, and is instead used as a partner drug for artemisinin combination therapy - Dihydroartemisinin PIPERAQUINE
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ARTEMISININ BASED COMBINATION THERAPY (ACT) Artemisinin compounds are shorter acting drugs Monotherapy needs to be extended beyond disappearance of parasite to prevent recrudescence Can be prevented by combining 3-5 day regimen with long acting drug like mefloquine 15 mg/kg single dose Indicated by WHO in acute uncomplicated resistant falciparum malaria
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Successful malaria control depends greatly on treatment with efficacious anti-malarial drugs Artemisinin compounds rapidly kill more than > 95 % of the plasmodia & only leave small biomass of the parasites to be killed by long t1/2 drugs Rapid clinical & parasitological cure High cure rates over 95% and low relapse rates Absence of resistance Good tolerability profile & simpler dosage regimen WHY COMBINATION THERAPY
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THE NEED FOR A COMBINATION THERAPY HENCE
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ACT REGIMENS IN USE Artesunate – Sulfadoxine, pyrimethamine: Adopted as first line in India under NMP Artesunate 100 mg BD for 3 days with S-P, 3 tablets Artesunate Mefloquine: By combining artesunate further spread of mefloquine resistance can be prevented Artesunate 100 mg BD for 3 days, + mefloquine 750 mg on second day & 500 mg on third day Artemether – Lumefantrine: First fixed-dose artemisinin-based combination therapy recommended and pre-qualified by WHO for the treatment of uncomplicated malaria caused by P. falciparum
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MALAPIP contains a fixed combination of two antimalarial active ingredients, dihydroartemisinin , an artemisinin derivative, & piperaquine. Both components are blood schizontocides One of the most widely used ACT One of five artemisinin‐based combination therapies the World Health Organization currently recommends to treat malaria Safe and effective for the treatment of multidrug-resistant uncomplicated malaria Good tolerability & no serious adverse Simple dosage regimen with OD dose convenience WHAT IS MALAPIP?
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MALAPIP Tablet: Each tablet contains Dihydroartemisinin 40mg + Piperaquine phosphate 320mg Tablets MALAPIP SUSPENSION: Each 5ml contains Dihydroartemisinin 5mg + Piperaquine phosphate 40mg Suspension COMPOSITION
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Absorption DHA is very rapidly absorbed, Tmax being approximately 1-2 hrs after single and multiple dosing. In patients, mean Cmax (CV %) & AUCINF of DHA (observed after the 1st dose) were 752 (47 %) ng/ml and 2,002 (45 %) ng/ml*h, respectively. DHA bioavailability appears to be higher in malaria patients than in healthy volunteers, possibly because malaria per se has an effect on DHA disposition. DIHYDROARTEMISININ ADME
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Distribution DHA is highly bound to human plasma proteins: the protein binding observed in in vitro studies was 44-93 % for DHA Observed to have a small volume of distribution in humans (0.8 l/kg; CV 35.5 %) DHA is principally converted to α-DHA-β-glucuronide (α-DHA-G). Studies in human liver microsomes showed that DHA was metabolised by the UDP-glucuronosyltransferase (UGT1A9 & UGT2B7) to α-DHA-G with no cytochrome P450-mediated metabolism. DIHYDROARTEMISININ ADME
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Elimination The elimination half-life of DHA is approximately 1 hour. The mean oral clearance for adult patients with malaria was 1.34 l/h/kg. Eliminated by metabolism (mainly glucuroconjugation). Its clearance was found to be slightly lower in female than in male healthy volunteers. DIHYDROARTEMISININ ADME
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Absorption Piperaquine, a highly lipophilic compound, is slowly absorbed. In humans, piperaquine has a Tmax of approximately 5 hours following a single and repeated dose. In patients mean (CV %) Cmax & AUC0-24 (observed after the first dose) were 179 (62 %) ng/ml and 1,679 (47 %) ng/ml*h, respectively. Due to its slow elimination, piperaquine accumulates in plasma after multiple doses with an accumulation factor of approximately 3. PIPERAQUINE - ADME
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Distribution Piperaquine is highly bound to human plasma proteins: the protein binding observed in in vitro studies was >99 % for piperaquine. Moreover, from in vitro and in vivo data in animals, piperaquine tends to accumulate in RBC. Pharmacokinetic parameters observed for piperaquine in humans indicate that this active substance has a large volume of distribution (730 l/kg; CV % 37.5 %). Mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 & CYP2C19 PIPERAQUINE - ADME
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Elimination The elimination half-life of piperaquine is around 22 days for adult patients and around 20 days for paediatric patients. The mean oral clearance for adult patients with malaria was 2.09 l/h/kg, while in paediatric patients was 2.43 l/h/kg. Due to its long elimination half-life, piperaquine accumulates after multiple dosing. PIPERAQUINE - ADME
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In – Treatment of uncomplicated falciparum malaria– Treatment of uncomplicated malaria due to other Plasmodium species, when chloroquine cannot be used– Completion treatment following parenteral therapy for severe malaria INDICATIONS
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DOSAGE MALAPIP TABLETS – 3 Tablets to be taken once daily for 3 days MALAPIP SUSPENSION – Child 5 to < 25 kg: 2.5 to 10 mg/kg daily of DHA + 20 to 32 mg/kg daily of PPQ– Child 25 kg and over and adult: 2 to 10 mg/kg daily of DHA + 16 to 27 mg/kg daily of PPQ
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Approved for medical use in Europe in 2011 Approved by more than 21 countries world wide & extensively used in SE Asia Listed on the World Health Organization's List of Essential Medicines as the safest & most effective medicines needed in a health system SALIENT FEATURES The RIGHT combination of antimalarial therapy DIHYDROARTEMISININ : Works very quickly to clear the malaria parasite from the person's blood PIPERAQUINE : A longer acting drug which clears the remaining parasites from the blood and may prevent new infections with malaria for several weeks
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Ensures a cure rate of 100% with 0 parasitemic patients on day LANCET endorses “ Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups & ensures good adherence without supervision” 73.7% patients cleared gametocytemia on day1 itself Reduces the risk of recurrent parasitemia within 4–9 weeks of treatment Faster fever clearance with median fever clearance time of 6 h SALIENT FEATURES
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SALIENT FEATURES Significant reduction in mean Plasmodium falciparum asexual parasite density (per microliter) of P. falciparum patients during the first 3 days after DP treatment
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SALIENT FEATURES SUPERIOR TO OTHER ANTIMALARIAL THERAPIES Significant reduction in P vivax gametocyte carriage in all patients studied after treatment with artemether-lumefantrine or dihydroartemisinin-piperaquine
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SALIENT FEATURES SUPERIOR TO OTHER ANTIMALARIAL THERAPIES Better Hb & Haematological recovery after treatment for patients receiving dihydroartemisinin-piperaquine than artemether-lumefantrine
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SALIENT FEATURES SUPERIOR TO OTHER ANTIMALARIAL THERAPIES Superior to artemether-lumefantrine at preventing further parasitaemia Reduces overall treatment failure compared to artemether-lumefantrine A suitable alternative to artesunate-mefloquine in terms of safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum Associated with less nausea, vomiting, dizziness, sleeplessness, and palpitations compared to artesunate plus mefloquine & no cardiac arrhythmias P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL
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PRODUCT ATTRIBUTES MALAPIP TABLETS Dihydroartemisinin 40mg + Piperaquine phosphate 320mg Tablets Available as Tablets Available in blisters of 9 Tablets
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PRODUCT ATTRIBUTES MALAPIP SUSPENSION Dihydroartemisinin 5mg + Piperaquine phosphate 40mg Suspension Available as Suspension Available in bottle of 60ml with a monocarton
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THANK - YOU